PTSD is a disabling condition consequent to trauma exposure. Recent evidence demonstrates PTSD secondary to combat exposure prospectively increases risk of early incident cardiovascular disease (CVD), with a meta-analyses we have recently completed revealing that PTSD is associated with a hazard ratio of 1.34 for incident CHD or CHD-specific mortality. The rate of PTSD among Veterans who have served during Operations Iraqi Freedom, Enduring Freedom, and New Dawn (OIF/OEF/OND) is more than double that seen in the non-veteran population and consistent with that previously seen among Vietnam era veterans. It is essential for purposes of risk stratification, risk reduction, and health services planning that we establisha more complete understanding of the illness burden associated with military service, and develop PTSD associated risk markers that predict early onset of CVD. Endothelial dysfunction is the earliest indicator of risk for incident CVD. In a pilot series with 23 OIF/OEF/OND veterans we have found that, compared to individuals without any symptoms of PTSD, those diagnosed with PTSD secondary to military service demonstrate significant impairment in endothelial function and that even those with sub-syndromal PTSD symptoms demonstrate impairment relative to those without symptoms. The Specific Aim of this proposed study is therefore to examine endothelial (dys) function as a promising mechanistic link between PTSD and risk for incident CVD. OIF/OEF veterans with a range of PTSD symptom severity (N=300) will complete our laboratory protocol that includes assessment of the endothelial response during standard hyperemic probe and during emotional stress, administered under controlled conditions, with the majority (N=230) repeating this protocol approximately 1 year late. Assessment of autonomic and HPA axis activity, and of contributors to vascular homeostasis (e.g., endothelin-1) will be accomplished during the protocol. We hypothesize that: 1) a diagnosis of PTSD will be associated with endothelial dysfunction; we will explore (1a) whether there is a dose response relationship such that, as severity of PTSD symptoms increase we observe greater endothelial dysfunction.; 2) A change in PTSD symptom severity from time 1 to time 2, will be associated with a concomitant change in the endothelial response to both hyperemic and emotional challenge. We will also explore the association of endothelial (dys) function during emotional stress with markers of sympathetic, parasympathetic, and HPA axis activity and with associated contributors to vascular homeostasis.